Associations of circulating C-reactive proteins, APOE ε4, and brain markers for Alzheimer’s disease in healthy samples across the lifespan

Wang, Yunpeng; Grydeland, Håkon; Roe, James M; Pan, Mengyu; Magnussen, Fredrik; Amlien, Inge K; Watne, Leiv Otto; Idland, Ane‐Victoria; Bertram, Lars; Gundersen, Thomas E.; Pascual‐Leone, Álvaro; Cabello‐Toscano, María; Tormos, José; Bartrés‐Faz, David; Drevon, Christian A.; Fjell, Anders M.; Walhovd, Kristine W

doi:10.1016/j.bbi.2021.12.008

Cited by 15 publications

(15 citation statements)

References 62 publications

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“…25,10,11 However, our findings are consistent with several studies that reported no associations between APOE genotype and brain volumes in younger age groups. 13,14,26 Other studies found increased cognitive performance and neuroimaging markers in the youngest populations (under 30), 12,27 consistent with the "antagonistic pleiotropy hypothesis," which postulates that a gene may have varying F I G U R E 1 Age-related curves for (A) nucleus accumbens, (B) hippocampus, (C) amygdala, (D) thalamus proper, and (E) medial orbitofrontal cortex for high and low Alzheimer's disease genetic risk score (AD-GRS). Predicted curves for 5th (low) versus 95th (high) percentile of AD-GRS (score including APOE variants is shown here).…”

Section: 8mentioning

confidence: 96%

“…Some prior studies in young adults suggested that AD genetic risk might confer life-long susceptibility to reduced hippocampal volume. [10][11][12] Conversely, two studies on the effects of APOE 𝜀4 haplotype on brain volume found no associations between the APOE 𝜀4 allele and brain volumes in younger age groups. 13,14 Few studies have comprehensively examined associations between AD-GRS and regional brain volumes in middle-aged and older adults to determine the precise timing of AD-related change.…”

Section: Introductionmentioning

confidence: 96%

“…AD‐GRS may also be associated with brain volume differences in relatively younger (preclinical) cohorts; however, evidence is mixed. Some prior studies in young adults suggested that AD genetic risk might confer life‐long susceptibility to reduced hippocampal volume 10–12 . Conversely, two studies on the effects of APOE

{{\varepsilon }}4

haplotype on brain volume found no associations between the APOE

{{\varepsilon }}4

allele and brain volumes in younger age groups 13,14 .…”

Section: Introductionmentioning

confidence: 99%

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Genetic risk score for Alzheimer's disease predicts brain volume differences in mid and late life in UK biobank participants

Buto,

Wang,

La Joie

et al. 2024

Alzheimer's & Dementia

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INTRODUCTIONWe estimated the ages when associations between Alzheimer's disease (AD) genes and brain volumes begin among middle‐aged and older adults.METHODSAmong 45,616 dementia‐free participants aged 45–80, linear regressions tested whether genetic risk score for AD (AD‐GRS) had age‐dependent associations with 38 regional brain magnetic resonance imaging volumes. Models were adjusted for sex, assessment center, genetic ancestry, and intracranial volume.RESULTSAD‐GRS modified the estimated effect of age (per decade) on the amygdala (−0.41 mm3 [−0.42, −0.40]); hippocampus (−0.45 mm3 [−0.45, −0.44]), nucleus accumbens (−0.55 mm3 [−0.56, −0.54]), thalamus (−0.38 mm3 [−0.39, −0.37]), and medial orbitofrontal cortex (−0.23 mm3 [−0.24, −0.22]). Trends began by age 45 for the nucleus accumbens and thalamus, 48 for the hippocampus, 51 for the amygdala, and 53 for the medial orbitofrontal cortex. An AD‐GRS excluding apolipoprotein E (APOE) was additionally associated with entorhinal and middle temporal cortices.DISCUSSIONAPOE and other genes that increase AD risk predict lower hippocampal and other brain volumes by middle age.

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Section: 8mentioning

confidence: 96%

Section: Introductionmentioning

confidence: 96%

{{\varepsilon }}4

haplotype on brain volume found no associations between the APOE

{{\varepsilon }}4

allele and brain volumes in younger age groups 13,14 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genetic risk score for Alzheimer's disease predicts brain volume differences in mid and late life in UK biobank participants

Buto,

Wang,

La Joie

et al. 2024

Alzheimer's & Dementia

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“…C‐reactive protein (CRP), for example, plays a key role in the systemic response to inflammation, and plasma CRP has been evaluated as a potential biomarker for AD 29 . However, elevated blood CRP level is associated with an increase in AD risk only in APOE ε4 carriers 30,31 …”

Section: Apolipoprotein E Biologymentioning

confidence: 99%

APOE and immunity: Research highlights

Kloske

Barnum²,

Batista

et al. 2023

Alzheimer's & Dementia

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INTRODUCTION:At the Alzheimer's Association's APOE and Immunity virtual conference, held in October 2021, leading neuroscience experts shared recent research advances on and inspiring insights into the various roles that both the apolipoprotein E gene (APOE) and facets of immunity play in neurodegenerative diseases, including Alzheimer's disease and other dementias. METHODS:The meeting brought together more than 1200 registered attendees from 62 different countries, representing the realms of academia and industry. RESULTS:During the 4-day meeting, presenters illuminated aspects of the cross-talk between APOE and immunity, with a focus on the roles of microglia, triggering receptor expressed on myeloid cells 2 (TREM2), and components of inflammation (e.g., tumor necrosis factor α [TNFα]).DISCUSSION: This manuscript emphasizes the importance of diversity in current and future research and presents an integrated view of innate immune functions in Alzheimer's disease as well as related promising directions in drug development.

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“…In addition, robust evidence supports that both brain neuroin ammation and peripheral low-grade in ammation (e.g., interleukin-6 [IL-6]; interleukin-8 [IL-8], and tumor necrosis factor alpha [TNF-α]) are involved in the pathogenesis of neurodegeneration and AD [12,13]. Data from a subsample of the Ginkgo Evaluation of Memory Study of cognitively unimpaired older adults showed that peripheral in ammatory biomarkers (e.g., IL-6 and C-reactive protein) were correlated with brain markers of Aβ deposition [14].…”

mentioning

confidence: 99%

Objectively-measured movement behaviors, systemic low-grade inflammation, and plasma neurofilament light chain in older adults: a population-based study

Wang

Han

et al. 2022

Preprint

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Background Evidence has linked self-reported sedentary behavior (SB) and physical activity (PA) with cognitive impairment; however, the underlying neuropathological mechanisms are poorly understood. We examined the dose-response associations of the accelerometer-measured daily SB and PA time with plasma neurofilament light chain (NfL) among older adults and the role of systemic low-grade inflammation in the associations. Methods This population-based study included 1,029 dementia-free older adults (age ≥ 60 years, 59.48% women) who undertook the ActiGraph substudy (March 2018-December 2020) in MIND-China. Plasma NfL and serum cytokines were measured on SIMOA and MSD platforms, respectively. Movement parameters were assessed with an accelerometer. Data were analyzed using the restricted cubic splines, general linear, and mediation models. Results There were J-shaped associations of daily SB and PA time with plasma NfL concentration, such that more daily SB time or less daily light-intensity physical activity (LPA) and moderate-to-vigorous-intensity physical activity (MVPA) time were significantly associated with increased plasma NfL only when SB time ≥ 8.00 hours/day or LPA time < 5.00 hours/day or MVPA time < 2.00 hours/day. Furthermore, more daily SB time or less daily LPA and MVPA time was significantly associated with higher serum inflammation scores (P < 0.05). Finally, serum biomarkers of low-grade inflammation could account for 15–19% of the associations between movement behaviors and plasma NfL level. Conclusions More daily SB and less PA time are associated with peripheral biomarker for neurodegeneration and systemic low-grade inflammation in older adults. The association of movement behaviors with neurodegeneration is partially mediated by systemic low-grade inflammation.

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Associations of circulating C-reactive proteins, APOE ε4, and brain markers for Alzheimer’s disease in healthy samples across the lifespan

Cited by 15 publications

References 62 publications

Genetic risk score for Alzheimer's disease predicts brain volume differences in mid and late life in UK biobank participants

Genetic risk score for Alzheimer's disease predicts brain volume differences in mid and late life in UK biobank participants

APOE and immunity: Research highlights

Objectively-measured movement behaviors, systemic low-grade inflammation, and plasma neurofilament light chain in older adults: a population-based study

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